This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Women are disproportionately affected by the AIDS pandemic globally. In the absence of an effective HIV vaccine, there is a critical need for developing female-controlled biomedical interventions, such as anti-HIV vaginal gels or rings, which can enable women to protect them from acquiring HIV. The CAPRISA 004 study, a phase IIb clinical trial, demonstrated for the first time that a vaginal gel containing the reverse transcription inhibitor Tenofovir (TFV) was safe and effective for reducing HIV infection in women. These findings support the data generated under this protocol, which showed that gels containing 1% TFV was completely protective against vaginal transmission of simian-HIV in macaques. Follow-up studies evaluating the window of protection in macaques revealed that TFV provided durable protection for up to 3 days and that the protection was associated with high TFV levels in vaginal tissues. Additional studies are now underway to assess the efficacy of TFV gels against vaginal transmission of drug-resistant viruses. Furthermore, this protocol also supported projects evaluating gels formulated with integrase inhibitors and showed them to be highly protective for both pre- and post exposure prophylaxis. In addition to gels, we have conducted pharmacokinetic studies in macaques to evaluate TFV release from intravaginal rings (IVRs). This device is designed to deliver sustained drug levels over weeks from a single application. These animal studies have been instrumental in advancing the field by highlighting the high effectiveness of topical antiretroviral prophylaxis and will continue to aid in future clinical trial designs.